Project Summary Yale Cancer Center's continuing participation in the NCTN under the leadership of Dr. Charles Fuchs includes not only a solid history of strong and committed accrual to NCTN trials, but strong leadership in the trials efforts at SWOG and other groups. YCC remains committed to prioritizing NCTN trials at all the YCC clinical centers and demonstrates annual accrual beyond estimates developed in our current U10 award. For this current submission, the vision of the YCC leadership is to: 1) continue to prioritize NCTN trials for accrual and develop YCC as a major contributor to group trials with additional contribution of our Care Centers; 2) facilitate and encourage YCC faculty to assume leadership roles in SWOG and other NCTN groups by supporting their time and effort and rewarding these activities; and 3) leverage our NCTN Coordinating Committee (NCC) as a bridge to bring Yale translational science to group activities as the results of our investigator initiated pilot trials become promising for multi-center and randomized questions. In addition to the leadership efforts of Dr. Fuchs, other key SWOG leaders include Drs. Roy Herbst, Daniel Petrylak and Lajos Pusztai. Drs. Peter Glazer, Roy Decker and Alessandro Santin will lead our efforts in the NRG group in addition to Dr. Barbara Burtness who will continue to lead our efforts in the ECOG-ACRIN group. We believe that the science and translational work at YCC has strong potential for incorporation into NCTN programs. Continued work on early phase drug development, EGFR resistance, PD-1 signaling, chemical biology, and new targets in signal transduction through the scientific programs of YCC have strong potential for translation into group trials. Furthermore, with expansion of the Smilow Cancer Hospital Care Centers, we demonstrated a greater opportunity to bring NCTN trials to the greater patient population across the state of Connecticut. This UG1 grant will assist us in developing the appropriate leadership and infrastructure for support of key NCTN group efforts in both accrual and program development.